Infant-type hemispheric glioma

Summary

Infant-type hemispheric glioma (MONDO:0858940) is a cancer with 2 cohort genes (1 CIViC-evidence somatic driver; 2 ClinVar predisposition records) and 1 clinical trial. Top therapeutic interventions include lorlatinib.

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	infant-type hemispheric glioma
Mondo ID	MONDO:0858940
Orphanet	695136
DOID	DOID:0081278
NCIT	C185471
UMLS	C5669919
MedGen	1806401
GARD	0026636
Is cancer (heuristic)	yes

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › glioma › astrocytic tumor › infant-type hemispheric glioma

Related subtypes (7): adult astrocytic tumor, childhood astrocytic tumor, gliofibroma, high grade astrocytic tumor, astrocytoma (excluding glioblastoma), low grade astrocytic tumor, anaplastic pleomorphic xanthoastrocytoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
55656	NM_007294.4(BRCA1):c.65T>C (p.Leu22Ser)	BRCA1	Pathogenic	reviewed by expert panel
5294	NM_001048174.2(MUTYH):c.1103G>A (p.Gly368Asp)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
MUTYH	Orphanet:247798	MUTYH-related polyposis
MUTYH	Orphanet:440437	Familial colorectal cancer Type X

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
MUTYH	HGNC:7527	ENSG00000132781	Q9UIF7	Adenine DNA glycosylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
MUTYH	Adenine DNA glycosylase	Involved in oxidative DNA damage repair.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
MUTYH	Other/Unknown	no		NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
MUTYH	134	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
MUTYH	1,815

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA1	P38398	33
MUTYH	Q9UIF7	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 64. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective MUTYH substrate binding	1	5710.0×	0.006	MUTYH
Defective MUTYH substrate processing	1	5710.0×	0.006	MUTYH
Defective DNA double strand break response due to BRCA1 loss of function	1	2855.0×	0.006	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	2855.0×	0.006	BRCA1
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	815.7×	0.016	BRCA1
Displacement of DNA glycosylase by APEX1	1	519.1×	0.017	MUTYH
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	475.8×	0.017	BRCA1
Diseases of DNA Double-Strand Break Repair	1	407.9×	0.017	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	407.9×	0.017	BRCA1
Resolution of D-Loop Structures	1	317.2×	0.017	BRCA1
Diseases of DNA repair	1	285.5×	0.017	BRCA1
DNA Double Strand Break Response	1	237.9×	0.017	BRCA1
Impaired BRCA2 binding to PALB2	1	228.4×	0.017	BRCA1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	211.5×	0.017	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	211.5×	0.017	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	211.5×	0.017	BRCA1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	196.9×	0.017	BRCA1
Homologous DNA Pairing and Strand Exchange	1	190.3×	0.017	BRCA1
Homology Directed Repair	1	154.3×	0.017	BRCA1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	154.3×	0.017	BRCA1
Impaired BRCA2 binding to RAD51	1	154.3×	0.017	BRCA1
Metalloprotease DUBs	1	150.3×	0.017	BRCA1
Resolution of D-loop Structures through Holliday Junction Intermediates	1	150.3×	0.017	BRCA1
HDR through Single Strand Annealing (SSA)	1	146.4×	0.017	BRCA1
Transcriptional Regulation by E2F6	1	146.4×	0.017	BRCA1
Meiosis	1	142.8×	0.017	BRCA1
Presynaptic phase of homologous DNA pairing and strand exchange	1	135.9×	0.017	BRCA1
DNA Double-Strand Break Repair	1	124.1×	0.018	BRCA1
Recognition and association of DNA glycosylase with site containing an affected purine	1	102.0×	0.020	MUTYH
Cleavage of the damaged purine	1	102.0×	0.020	MUTYH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
depurination	1	2106.5×	0.006	MUTYH
cellular response to indole-3-methanol	1	1685.2×	0.006	BRCA1
chordate embryonic development	1	1404.3×	0.006	BRCA1
negative regulation of centriole replication	1	1203.7×	0.006	BRCA1
DNA strand resection involved in replication fork processing	1	1053.2×	0.006	BRCA1
DNA damage tolerance	1	842.6×	0.006	BRCA1
homologous recombination	1	702.2×	0.006	BRCA1
negative regulation of intracellular estrogen receptor signaling pathway	1	561.7×	0.006	BRCA1
regulation of DNA damage checkpoint	1	561.7×	0.006	BRCA1
negative regulation of gene expression via chromosomal CpG island methylation	1	526.6×	0.006	BRCA1
negative regulation of necroptotic process	1	495.6×	0.006	MUTYH
protein K6-linked ubiquitination	1	495.6×	0.006	BRCA1
random inactivation of X chromosome	1	468.1×	0.006	BRCA1
negative regulation of reactive oxygen species metabolic process	1	468.1×	0.006	BRCA1
negative regulation of fatty acid biosynthetic process	1	443.5×	0.006	BRCA1
DNA repair	2	63.8×	0.006	BRCA1, MUTYH
mitotic G2/M transition checkpoint	1	401.2×	0.007	BRCA1
mismatch repair	1	324.1×	0.008	MUTYH
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	290.6×	0.008	BRCA1
positive regulation of vascular endothelial growth factor production	1	247.8×	0.009	BRCA1
base-excision repair	1	234.1×	0.009	MUTYH
mitotic G2 DNA damage checkpoint signaling	1	221.7×	0.009	BRCA1
response to ionizing radiation	1	205.5×	0.009	BRCA1
cellular response to ionizing radiation	1	205.5×	0.009	BRCA1
positive regulation of DNA repair	1	179.3×	0.010	BRCA1
fatty acid biosynthetic process	1	175.5×	0.010	BRCA1
centrosome cycle	1	168.5×	0.010	BRCA1
intrinsic apoptotic signaling pathway in response to DNA damage	1	162.0×	0.010	BRCA1
negative regulation of cell cycle	1	145.3×	0.011	BRCA1
regulation of DNA repair	1	138.1×	0.011	BRCA1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA1	12	4
MUTYH	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BRCA1	13	Binding:9, Functional:4
MUTYH	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

12 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BRCA1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MUTYH

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MUTYH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06333899	EARLY_PHASE1	RECRUITING	Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LORLATINIB	4	1
CHEMBL4303155	0	1
CHEMBL4436406	0	1
CHEMBL5289235	0	1